key: cord-0712454-8176q9lv
authors: Akuffo-Addo, Edgar; Nicholas, Mathew N.; Joseph, Marissa
title: COVID-19 Skin Manifestations in Skin of Colour
date: 2021-10-19
journal: J Cutan Med Surg
DOI: 10.1177/12034754211053310
sha: 01b6a71da389f6cfce060f2bc292668cdb41468f
doc_id: 712454
cord_uid: 8176q9lv

Coronavirus disease (COVID-19) skin manifestations have been increasingly reported in medical literature. Recent discussions have identified a lack of images of skin of color (SOC) patients with COVID-19 related skin findings despite people with skin of color being disproportionately affected with the disease. There have been calls to prioritize the identification of COVID-19 skin manifestations in patients with SOC and disseminate these findings. The objective of this article is to review the existing literature on COVID-19 skin manifestations and, where possible, discuss how they may present differently in patients with SOC. Further research is needed to allow primary care physicians and dermatologists to be aware of and easily identify patients with cutaneous findings that may be secondary to COVID-19. Patients presenting with idiopathic dermatologic manifestations should be considered for COVID-19 testing and follow public health guidelines for self-isolation.

The initial cases of Coronavirus disease (COVID-19), a disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), were first reported in China in December 2019. 1 The disease has grown to become a global pandemic withover120millionconfirmedcasestodate. 2 Canada reported its first case of COVID-19 in January 2020 and has since recordedover960,000confirmedcases. 3, 4 Most of the reported cases have been in Canada's two most populous provinces, Quebec and Ontario. The two provinces account for approximately 70% of the total cases in Canada and represent 62% of the country's population. 4 Comprehensive race-based COVID-19 data are currently limited in Canada. According to the latest data released in December 2020 by the Toronto Public Health Unit, Ontario, racialized persons account for 77% of reported COVID-19 cases while only representing half of the city's population. 5 COVID-19isamultisystemdiseaseaffectingseveralvital organs. 6 Although the cutaneous manifestations of COVID-19 do not present in all infected patients, physicians must be aware of the skin manifestations linked to COVID-19 as they might be the presenting sign of infection in asymptomatic or minimally symptomatic patients. They may also be a useful prognostic marker for disease severity. 7 Healthcare providers should be able to identify these COVID-19 related cutaneous manifestations in patients of all skintypes.WhilethescientificliteratureonCOVID-19cutaneous manifestations continue to grow, there is a paucity of clinical images of skin of color (SOC) patients in medical publications. According to a systematic review of Englishlanguage articles published between 31 December 2019 and 3 May 2020, the authors found there were no clinical images representing Fitzpatrick type V or VI skin in the published articles. 8 Since patients with SOC may have subtle disease presentation anddifferentmorphologicvariants, 9 the lack of representation of images of skin color may delay a diagnosis and result in patients with SOC receiving suboptimal care. 10, 11 A prospective study done at the India Institute of Medical Sciences to study the prevalence of cutaneous manifestations in COVID-19 infected patients presenting at the center concluded that the reported vascular cutaneous manifestations, such as chilblain-like lesions, vasculitis and livedo reticularis were uncommon among patients with darker skin phototypes. 12 Similarly, a study in Brazil found that patients with non-white skin rarely presented with chilblainlike lesions. 13 Generally, the presentation and manifestation of any cutaneous pathology can vary widely with skin tone. Inflammatory skinconditionscanpresentdifferentlyindarkerskincompared tolighterskin.Indarkerskin,inflammationismoresubtleand presents with pigmentary change and violaceous colouration. Thisisincontrasttolighterskinwhereinflammationismore noticeable and typically presents as erythema. 14, 15 COVID-19 skin manifestations are no different and SOC patients can present with more subtle dermatoses compared to white skin. Considering the variability of skin findings presented by COVID-19 patients and how COVID-19 has disproportionately affected people of color, 16 it is particularly important that healthcare providers are able to identify how the cutaneous manifestations of COVID-19 may present in SOC patients.

Our review will summarize the key information that is currently known about the COVID-19 cutaneous manifestations and characterize how these may present in patients with SOC.

A literature search was conducted in PubMed and Google Scholar databases for articles written in English. There were no date restrictions but we concluded our search in March 2021. Search terms included "darker skin", "skin of color," and "skin manifestations" in combination with "COVID-19" and "SARS-CoV-2." We explored the bibliography sections of each retrieved article to identify other useful references. Due to the paucity of literature on this topic, we scanned other forms of grey literature, mostly published books on skin of color and the British Association of Dermatology website, along with using personal clinical experiences for diagnostic pearls and images.

The prevalence of COVID-19 skin manifestations remains unknown with varying prevalence being reported in the literature. A large Chinese study of 1099 COVID-19 patients reported an incidence rate of 0.2% while a study of 88 COVID-19 patients by a dermatologist in Italy reported an incidence rate of 20.4%. 17 The cutaneous manifestations of COVID-19 have been documented in patients of all ages, from as early as 2 months to 89 years. 18 Due to the polymorphous nature of the COVID-19 skin manifestations, several pathophysiological mechanisms have been postulated. The etiology and pathophysiology of these skin manifestations continue to evolve. In general, the skin manifestations are beingattributedtotheoveractivationofinflammatorymediators leading to a cytokine storm and damage to the endothelium. 19 Direct viral effect on the endothelium and viral-induced vasculitis play a predominant role in the cutaneous manifestations seen in COVID-19 patients. 20 Although the COVID-19 cutaneous manifestations are polymorphousinnature,Genoveseetal.recentlyclassified the cutaneous manifestations into six main clinical patterns: (i) urticarial rash, (ii) confluent erythematous/maculopapular/morbilliform rash, (iii) papulovesicular exanthem, (iv) chilblain-like lesions, (v) livedo reticularis/racemose-like pattern, and (vi) purpuric "vasculitic" pattern. 21 Adopting andmodifyingthisclassification,weprovideanoverviewof the cutaneous manifestations associated with COVID-19, while focusing on how the cutaneous manifestations may present on patients with SOC. This overview as well as treatments for each manifestation is summarized in Table 1 .

(I) Urticarial rash. Among the six clinical patterns listed above, urticaria is the second most common skin manifestation that has been reported in COVID-19 patients. 18 Most patients present with urticarial eruption during the active symptomatic phase of the infection. 18 However, in some cases, the eruption precedes other classical symptoms of COVID-19. 22 In COVID-19 patients, urticaria affects the skin and mucous membrane. It presents as an erythematous and pruritic rash with or without angioedema as well. 23 For most patients with COVID-19, the urticarial rash is self-limiting and disappears or clinically improves within a week. However, the rash can be managed with either a combination of oral antihistamines and oral steroids. In patients with chronic urticaria, antihistamines alone are predominantly usedwithgoodefficacy,whilelow-dosesystemiccorticosteroids either in conjunction or used alone were also effective. 22 While urticaria is a common skin manifestation in lighter skin patients with COVID-19, data on prevalence in SOC patients is lacking. There have been no reports of morphological differencesinpatientswithSOCasofMarch2021.However, there have been few cases reported of African American patients hospitalized for COVID-19 developing angioedema of the face, lips, mouth and tongue without urticaria. 24 On SOC patients, the hives may be the same color as the surrounding skin and the erythemathatoftensurroundsurticarialrashmaybedifficultto appreciate, as iillustrated in Figure 1 . Examining the skin for enlarged follicular openings with increased distance between them is useful in establishing dermal edema. 25 A tactile approach canbebeneficialaschangesinskintextureorraisedbumpscan also prompt a physician to a rash that is not readily visible. Treatment of urticarial rash in patients with SOC follows the standard principles of therapy described above.

(II) Maculopapular rash. Maculopapular rash is reported as one of the most common cutaneous manifestation in COVID-19 patients. 26 The majority of patients presented with the maculopapular rash during the symptomatic phase of their infection, at the same time as the onset of other non-cutaneous COVID-19 symptoms. However, the rash was also present in asymptomatic COVID-19 patients. 7 Maculopapular eruptions encompass a broad category of primary morphologies. As such, the classification of maculopapular rashes actually encompasses macular erythema and morbilliform exanthems. 27 This presentation is typically localized to the trunk and extremities with pruritus in most patients, as illustrated in Figure 2 . Topical corticosteroidsaresufficientinmanagingmostcases.Insevere cases with widespread presentation, systemic corticosteroids may be indicated. 21 A self-reported study from Brazil found the prevalence of morbilliform exanthem to be 4% in COVID-19 patients with non-white skin. 13 In SOC patients, erythema can translate into hyperpigmentation.Theincreaseinpigmentmaymakeitdifficult to recognize the erythema. 28 As a result, it is possible for SOCpatientstopresentwithavaryingshadeofred.Toconfirm inflammationinSOCpatients,onecantouchtheskintocheck if the skin is warm or hot to the touch. Palpation is an underestimated examination modality but assessing the skin for scale, texturalchanges,sweatingdifferencesandtemperaturecanprovide clues to an underlying dermatological condition. 29 In darker skin, lichenification occurs readily. 30 Due to the pruritus associated with COVID-19 maculopapular rash, SOC patientsmaypresentwithsomelichenification.Thethickened skin is often darker than surrounding skin. This darkening is more apparent in dark-skinned patients. While treatment of COVID-19 related morbilliform eruptions in SOC patients followsthestandardprinciplesoftherapyabove,specificconsiderations exist. SOC patients frequently experience post inflammatoryhyperpigmentationafteraninflammatoryinjury resolves. Early treatment of the hyperpigmentation with topical depigmenting agents may hasten its resolution. 28 (III) Psoriasiform Dermatoses. Cases of pityriasis rosea-like manifestations have also been reported in COVID-19 positive patients. [31] [32] [33] Patients initially present with a herald patch with scaling collarette followed by widespread erythematoussquamous rash of varying morphology and size. 31, 34 There have been cases reported of a pityriasis rosea-like rash without an associated plaque or herald patch. 32 Most patients with pityriasis rosea-like manifestations were asymptomatic for COVID-19. 31, 32 The rash is self-limiting and completely resolves within two to 4 weeks. The associated pruritus can be managed with a potent topical corticosteroid. 31, 32 The erythematous appearance of pityriasis rosea rash typically seen in lighter skin may not be encountered in SOC. 35 In SOC, the exanthem may have a gray, dark brown, or even black appearance as the erythema associated with this presentation may not be readily noticeable. Paying close attention for scaling inSOCmaybebeneficialasthereisgreatervisibilityofwhite patchy and peripheral collarette scales, as illustrated in Figure 3 . 31 (IV) Papulovesicular exanthem. The papulovesicular exanthem rash was initially described as a varicella-like eruption due to its similarity with lesions seen in varicella patients. However, the involvement of the trunk and scattered distribution of the lesions in addition to the absence of pruritus differentiates it from a varicella infection. 21 Some COVID-19 patients develop erythematous papules over the extremities resembling pseudo-vesicles. The skin lesions generally appear 3 days after the onset of systemic symptoms and is associated with moderate to severe COVID-19 severity. They heal after about 8 days without any scarring or post-inflammatorypigmentation. 36 Considering the rash is selflimiting in about a week, there are no standardized treatments for COVID-19 related papulovesicular exanthem. 21 However, high-potency topical corticosteroids have been used as treatment. 37 SOC patients may present with hyperpigmentation around the vesicles and papules. 25 The rash may be umbilicated with some crusting. While pruritus has not been reported widely in the literature, the few cases involving SOC had an associated pruritus. 31 As a result, linear excoriations may occur in SOC patients due to scratching, as illustrated in Figure 4 .

(V) Chilblain-like lesions. Asymptomatic carriers of the SARS-CoV-2 may present with chilblain-like lesions without any history of exposure to cold. The lesions present as erythematousviolaceous macules, plaques and nodules on the lateral aspects of thefeetandthedistalaspectsofthefingers.Themanifestationis more common in children and young adults. 38 This presentation has been termed "COVID toes", and is usually associated with mild COVID-19 disease severity representing the convalescent phase of infection. 39 While there are no treatment guidelines for COVID-19 patients presenting with chilblain-like lesions of the feet and hands, potent topical corticosteroids are most commonly recommended with supportive treatment. 40 A case series of 318 patients with chilblain-like lesions found that 0.7% of the cases were black or African American. 39 Similarly, a study in Brazil found that patients with non-white skin rarely presented with chilblain-like lesions. 13 However, when SOC patients present with chilblain-like lesions, they are more subtle. The red and pink hues are not readily visible. 11 Assess the patient for swelling as edema and swelling of the digits are more evident than the erythema, as illustrated in Figure 5 . 11, 41 Examine the heels and subungual regions for edematous pink plaques since they can progress into hyperpigmented plaques. 42 A tingling and burning sensation have been reported in some patients. 11 (VI) Livedo reticularis and racemosa. SARS-CoV-2 infected patients may present with livedo reticularis or racemosa, a lacelike pattern of unilateral erythematous and violaceous cutaneous discoloration of the lower limbs. Livedo reticularis is characteristic with ischemia of cutaneous capillaries. The prevalence of livedo reticularis-like and racemosa-like lesions have been reported to range from 0.6% to 3.5% of all COVID-19 cutaneous manifestations. 21 Although patients do not commonly present with livedo racemosa, if they do it is often associated with high disease severity and mortality. 43, 44 The livedo reticularis associated with COVID-19 disease is often transient and selfresolves within 24 hr without treatment. 18 In some patients it can persist for weeks and can progress into necrosis secondary to small vessel thrombosis. 36 There are no established therapeutic options for COVID-19 related livedo reticularis or racemosalike lesions. If there are concerns for thrombosis and ischemia, topical or systemic vasodilators, antiplatelets including low dose acetylsalicylic acid, or anticoagulants can be tried. 45 Studies have shown that vascular cutaneous manifestations are uncommon in darker skin types. 12, 46 While the literature may describe livedo reticularis as a reddish-blue discoloration, this may not be apparent in SOC. On SOC, an uneven distribution of melanin throughout the skin causes hyperpigmented patches that form the lace-like discoloration of the skin, as illustrated in Figure 6 . In addition, livedo reticularis/racemosa is more prominent when the patient is upright and may not be apparent if the patient is examined in the supine position. 47 (VII) Purpuric Pattern/Petechiae. Patients with SARS-CoV-2 may also present with purpuric lesions. These lesions can present either as generalized or localized petechial rash in the skin folds. They may evolve into hemorrhagic blisters and in severe cases can result in extensive acute necrosis, as illustrated in Figure 7 . 21 While they are not as common as the other skin manifestations, they have been reported to occur more frequently in elderly patients with severe COVID-19. 21 Among the cutaneous manifestations in the literature purpuric lesions have the highest rate of COVID-19 related mortality. 21 Topical moderate-potency corticosteroids can be used to manage mild cases of purpuric lesions. However, for severe cases with necrosis, systemic corticosteroids may be indicated. 21 A study in Brazil found that four percent of non-white skin patients with COVID-19 cutaneous manifestations presented with purpuric lesions. 13 In SOC patients, petechiae maybedifficulttoseeforanuntrainedeye.Lookforpetechiae in SOC patients by examining areas with lighter pigmentation. The small, reddish purple lesions may be more evident if present in the buccal mucosa of the mouth or conjunctiva of the eye. 48 One can also apply pressure to the area to check for blanching. While erythematous areas will blanch, petechiae or purpuric lesions will not. 49

By 2031, people with SOC could constitute one-third of Canada's population. 50 Disease presentation, treatment plan andsequelaeinSOCpatientscanbedifferentthanthoseof lighter skinned patients. 51 A thorough understanding of how skin conditions and variances may present in this group will enable physicians provide personalized care to SOC patients. Pigmentation is one of the clinically important variations one must consider when developing a plan of care for a SOC patient.Postinflammatoryhyperpigmentationisoftenprominent and prolonged in SOC. 52 Pigmentary abnormalities can have a negative impact on the quality of life for SOC patients. They are among the most common reasons why SOC patients seek dermatological care. 53 Generally, pigmentary changes including hyperpigmentation, hypopigmentation and polymorphic pigmentation are key indicators of an underlying or resolved dermatological condition. When unsure, a physician can ask patients about any changes in their skin since they may be able to detect very subtle changes in their own skin color. In SOC patients presenting with COVID-19 skin manifestations, preventive and therapeutic measures should be considered to manage any associated pigmentary changes. Medical therapy may not be needed in all patients presenting with postinflammatory hyperpigmentation since the condition improves with time. Early treatment of the hyperpigmentation with strict ultraviolet radiation avoidance, topical depigmenting agents such as hydroquinone and azelaic acid, as well as retinoids may hasten its resolution. 28

As new strains of SARS-CoV-2 emerge, scientists predict the coronavirus may become endemic. 53 Considering this, and the need to curtail the spread of this virus, knowledge of COVID-19 related cutaneous manifestations is important as physicians continue to screen patients for signs and symptoms of COVID-19. Healthcare professionals must recognize the cutaneous manifestations of COVID-19 and how they may present in SOC.

While the COVID-19 dermatology registries established by the American Academy of Dermatology (AAD) and the British Association of Dermatologists (BAD) have added to the number of published images that characterize COVID-19 cutaneous manifestations in SOC, their efforts need to be amplified. 54, 55 Collaboration with other national and international dermatologic societies, particularly in countries with a high proportion of people with SOC, to create their own registries could increase the number of available photos in literature. Furthermore, leveraging the skills of our colleagues in primary care and including them in these registries may also capture more COVID-19 patients with SOC who may not be seen by dermatologists.

Theauthor(s)declarednopotentialconflictsofinterestwithrespect totheresearch,authorship,and/orpublicationofthisarticle.

The author(s) received no financial support for the research, authorship,and/orpublicationofthisarticle.

EdgarAkuffo-Addo https://orcid.org/0000-0002-8867-0935 Mathew N. Nicholas https://orcid.org/0000-0002-2284-5835 MarissaJoseph https://orcid.org/0000-0002-7469-5082

First known person-to-person transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the USA. The Lancet

COVID-19 Coronavirus Pandemic

Government of Canada Web site

COVID-19): Outbreak update. Government of CanadaWeb site

COVID-19: Status of Cases in Toronto

Organ-specificmanifestationsofCOVID-19infection

Cutaneous manifestations of COVID-19: an evidence-based review

Absenceof images of skin of colour in publications of COVID-19 skin manifestations

Disparities in dermatology educational resources

Practice gaps. barriers in melanoma detection in ethnic minorities: comment on anatomic distribution of malignant melanoma on the non-Hispanic black patient

Pernio-likeeruptionassociatedwithCOVID-19inskin of color

Recognizable vascular skin manifestations of SARS-CoV-2 (COVID-19) infection are uncommon in patients with darker skin phototypes

Self-reported cutaneous manifestations in 1429 Brazilian COVID-19-infected patients

Dermatological conditions in skin of COLOR-: managing atopic dermatitis

Atopicdermatitis in diverse racial and ethnic groups-Variations in epidemiology, genetics, clinical presentation and treatment

Racial disparity of coronavirus disease 2019 in African American communities

A review of the dermatological manifestations of coronavirus disease

A comprehensive review of cutaneous manifestations associated with COVID-19

Are the cutaneous manifestations during or due to SARS-CoV-2 infection/COVID-19 frequent or not? Revision of possible pathophysiologic mechanisms

Skin manifestations in COVID-19 provide a clue for disease's pathophysiology understanding

Skin manifestations associated with COVID-19: current knowledge and future perspectives

Urticaria and COVID-19: a review

Management of urticaria in COVID-19 patients: a systematic review. Dermatol Ther

Ethnic Dermatology

Cutaneous manifestations in confirmed COVID-19 patients: a systematic review

Maculopapular eruptions associated to COVID-19: a subanalysis of the COVID-Piel study

Postinflammatory hyperpigmentation: a review of the epidemiology, clinical features, and treatment options in skin of color

Palpation of the skin--an important issue

An illustrated guide to dermatoses in dark skin

Pityriasis rosea in otherwise asymptomatic confirmed COVID-19-positive patients: a report of 2 cases

Pityriasis rosea Gibert type rash in an asymptomatic patient that tested positive for COVID-19

Prolonged dermatological manifestation 4 weeks following recovery of COVID-19 in a child

Pityriasis rosealike eruption revealing COVID-19

Pityriasis rosea in the Sudan

Cutaneous manifestations of coronavi-rusdisease2019in458confirmedcases:asystematicreview

Papular-purpuric exanthem in a COVID-19 patient: clinical and dermoscopic description

Characterization of acute acral skin lesions in nonhospitalized patients: a case series of 132 patients during the COVID-19 outbreak

Pernio-like skin lesions associated with COVID-19: a case series of 318 patients from 8 countries

Chilblains-like lesions and SARS-CoV-2 in children: an overview in therapeutic approach

Erythematous-edematous type of chilblain-like lesions and COVID-19: an Indian perspective

Chilblains in children in the setting of COVID-19 pandemic. Pediatr Dermatol

Cutaneous manifestations in adult patients with COVID-19 and dermatologic conditions related to the COVID-19 pandemic in health care workers

Cutaneous manifestations in patients with COVID-19: a preliminary review of an emerging issue

Anewrashdifferential:CoVID-19

Cutaneous eruption in COVID-19-infected patients in Thailand: an observational descriptive study

Livedo reticularis: an underutilized diagnostic clue in cholesterol embolization syndrome

Oral manifestations of COVID-19 disease: a review article

Portable Signs & Symptoms. Wolters Kluwer Health

Ethnic diversity and immigration Statistics Canada Web site

Meeting the unique dermatologic needs of black patients

Fitzpatrick's dermatology in general medicine, 8e. 8th ed. McGraw-Hill Education LLC

The coronavirus is here to stay -here's what that means

The American Academy of dermatology COVID-19 registry: Crowdsourcing dermatology in the age of COVID-19

British Association of Dermatologists COVID-19 Skin Patterns

Cutaneous man-ifestationsofCOVID-19inskinofcolor:afirsthandperspective of three cases in a tertiary care center in India

Cutaneousfindings in hospitalized and critically ill patients with COVID-19: a case series of 15 patients

The spectrum of COVID-19-associated dermatologic manifestations: an international registry of 716 patients from 31 countries